Showing papers by "University of Louisville published in 2006"

Safety and Efficacy of a Pentavalent Human–Bovine (WC3) Reassortant Rotavirus Vaccine

Abstract: BACKGROUND: Rotavirus is a leading cause of childhood gastroenteritis and death worldwide. METHODS: We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive ...

Student Engagement and Student Learning: Testing the Linkages.

Abstract: This study examines (1) the extent to which student engagement is associated with experimental and traditional measures of academic performance, (2) whether the relationships between engagement and academic performance are conditional, and (3) whether institutions differ in terms of their ability to convert student engagement into academic performance. The sample consisted of 1058 students at 14 four-year colleges and universities that completed several instruments during 2002. Many measures of student engagement were linked positively with such desirable learning outcomes as critical thinking and grades, although most of the relationships were weak in strength. The results suggest that the lowest-ability students benefit more from engagement than classmates, first-year students and seniors convert different forms of engagement into academic achievement, and certain institutions more effectively convert student engagement into higher performance on critical thinking tests.

Comorbid Psychiatric Disorders in Children with Autism: Interview Development and Rates of Disorders

Abstract: The Kiddie Schedule for Affective Disorders and Schizophrenia was modified for use in children and adolescents with autism by developing additional screening questions and coding options that reflect the presentation of psychiatric disorders in autism spectrum disorders. The modified instrument, the Autism Comorbidity Interview-Present and Lifetime Version (ACI-PL), was piloted and frequently diagnosed disorders, depression, ADHD, and OCD, were tested for reliability and validity. The ACI-PL provides reliable DSM diagnoses that are valid based on clinical psychiatric diagnosis and treatment history. The sample demonstrated a high prevalence of specific phobia, obsessive compulsive disorder, and ADHD. The rates of psychiatric disorder in autism are high and are associated with functional impairment.

Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery.

Abstract: Membrane-derived vesicles (MV) are released from the surface of activated eucaryotic cells and exert pleiotropic effects on surrounding cells. Since the maintenance of pluripotency and undifferentiated propagation of embryonic stem (ES) cells in vitro requires tight cell to cell contacts and effective intercellular signaling, we hypothesize that MV derived from ES cells (ES-MV) express stem cell-specific molecules that may also support self-renewal and expansion of adult stem cells. To address this hypothesis, we employed expansion of hematopoietic progenitor cells (HPC) as a model. We found that ES-MV (10 microg/ml) isolated from murine ES cells (ES-D3) in serum-free cultures significantly (i) enhanced survival and improved expansion of murine HPC, (ii) upregulated the expression of early pluripotent (Oct-4, Nanog and Rex-1) and early hematopoietic stem cells (Scl, HoxB4 and GATA 2) markers in these cells, and (iii) induced phosphorylation of MAPK p42/44 and serine-threonine kinase AKT. Furthermore, molecular analysis revealed that ES-MV express Wnt-3 protein and are selectively highly enriched in mRNA for several pluripotent transcription factors as compared to parental ES cells. More important, this mRNA could be delivered by ES-MV to target cells and translated into the corresponding proteins. The biological effects of ES-MV were inhibited after heat inactivation or pretreatment with RNAse, indicating a major involvement of protein and mRNA components of ES-MV in the observed phenomena. We postulate that ES-MV may efficiently expand HPC by stimulating them with ES-MV expressed ligands (e.g., Wnt-3) as well as increase their pluripotency after horizontal transfer of ES-derived mRNA.

Clinical applications of cone-beam computed tomography in dental practice.

Abstract: Cone-beam computed tomography (CBCT) systems have been designed for imaging hard tissues of the maxillofacial region. CBCT is capable of providing sub-millimetre resolution in images of high diagnostic quality, with short scanning times (10-70 seconds) and radiation dosages reportedly up to 15 times lower than those of conventional CT scans. Increasing availability of this technology provides the dental clinician with an imaging modality capable of providing a 3-dimensional representation of the maxillofacial skeleton with minimal distortion. This article provides an overview of currently available maxillofacial CBCT systems and reviews the specific application of various CBCT display modes to clinical dental practice.

Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication.

Abstract: Normal and malignant cells shed from their surface membranes as well as secrete from the endosomal membrane compartment circular membrane fragments called microvesicles (MV). MV that are released from viable cells are usually smaller in size compared to the apoptotic bodies derived from damaged cells and unlike them do not contain fragmented DNA. Growing experimental evidence indicates that MV are an underappreciated component of the cell environment and play an important pleiotropic role in many biological processes. Generally, MV are enriched in various bioactive molecules and may (i) directly stimulate cells as a kind of 'signaling complex', (ii) transfer membrane receptors, proteins, mRNA and organelles (e.g., mitochondria) between cells and finally (iii) deliver infectious agents into cells (e.g., human immuno deficiency virus, prions). In this review, we discuss the pleiotropic effects of MV that are important for communication between cells, as well as the role of MV in carcinogenesis, coagulation, immune responses and modulation of susceptibility/infectability of cells to retroviruses or prions.

Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis

Abstract: Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens.

The influence of bio-behavioural factors on tumour biology: pathways and mechanisms

Abstract: Stress does not cause cancer per se, but depression and a lack of social support might influence cancer progression and clinical outcome. Can identification of the molecular and biological mechanisms involved be used to improve patient treatment? Epidemiological studies indicate that stress, chronic depression and lack of social support might serve as risk factors for cancer development and progression. Recent cellular and molecular studies have identified biological processes that could potentially mediate such effects. This review integrates clinical, cellular and molecular studies to provide a mechanistic understanding of the interface between biological and behavioural influences in cancer, and identifies novel behavioural or pharmacological interventions that might help improve cancer outcomes.

A population of very small embryonic-like (VSEL) CXCR4 + SSEA-1 + Oct-4 + stem cells identified in adult bone marrow

Abstract: By employing multiparameter sorting, we identified in murine bone marrow (BM) a homogenous population of rare (approximately 0.02% of BMMNC) Sca-1(+)lin(-)CD45- cells that express by RQ-PCR and immunohistochemistry markers of pluripotent stem cells (PSC) such as SSEA-1, Oct-4, Nanog and Rex-1. The direct electronmicroscopical analysis revealed that these cells are small (approximately 2-4 microm), posses large nuclei surrounded by a narrow rim of cytoplasm, and contain open-type chromatin (euchromatin) that is typical for embryonic stem cells. In vitro cultures these cells are able to differentiate into all three germ-layer lineages. The number of these cells is highest in BM from young (approximately 1-month-old) mice and decreases with age. It is also significantly diminished in short living DBA/2J mice as compared to long living B6 animals. These cells in vitro respond strongly to SDF-1, HGF/SF and LIF and express CXCR4, c-met and LIF-R, respectively, and since they adhere to fibroblasts they may be coisolated with BM adherent cells. We hypothesize that this population of Sca-1(+)lin(-)CD45- very small embryonic-like (VSEL) stem cells is deposited early during development in BM and could be a source of pluripotent stem cells for tissue/organ regeneration.

Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion

Abstract: Study design A retrospective review of patients who underwent an anterior cervical fusion using recombinant human bone morphogenetic protein (rhBMP)-2 with an absorbable collagen sponge (INFUSE; Medtronic Sofamor Danek, Minneapolis, MN). Objective To ascertain the complication rate after the use of high-dose INFUSE in anterior cervical fusions. Summary of background data The rhBMP-2 has been primarily investigated in lumbar spine fusions, where it has significantly enhanced the fusion rate and decreased the length of surgery, blood loss, and hospital stay. Methods We present 151 patients who underwent either an anterior cervical discectomy and fusion (n = 138) or anterior cervical vertebrectomy and fusion (n = 13) augmented with high-dose INFUSE between July 2003 and March 2004. The rhBMP-2 (up to 2.1 mg/level) was used in the anterior cervical discectomy and fusions. Results A total of 35 (23.2%) patients had complications after the use of high-dose INFUSE in the cervical spine. There were 15 patients diagnosed with a hematoma, including 11 on postoperative day 4 or 5, of whom 8 were surgically evacuated. Thirteen individuals had either a prolonged hospital stay (> 48 hours) or hospital readmission because of swallowing/breathing difficulties or dramatic swelling without hematoma. Conclusions A significant rate of complications resulted after the use of a high dose of INFUSE in anterior cervical fusions. We hypothesize that in the cervical area, the putative inflammatory effect that contributes to the effectiveness of INFUSE in inducing fusion may spread to adjacent critical structures and lead to increased postoperative morbidity. A thorough investigation is warranted to determine the optimal dose of rhBMP-2 that will promote cervical fusion and minimize complications.

Smoking and Inflammatory Bowel Disease: A Meta-analysis

Abstract: OBJECTIVE To assess whether there is a true effect of smoking on the 2 most prevalent forms of inflammatory bowel disease (IBD): Crohn disease (CD) and ulcerative colitis (UC). METHODS For this meta-analysis, we searched multiple health care databases, including MEDLINE and EMBASE (January 1980 to January 2006), to examine the relationship between smoking and IBD. Keywords searched included smoking, inflammatory bowel disease, Crohn's disease , and ulcerative colitis . Data were abstracted using predefined inclusion and exclusion criteria. An odds ratio (OR) was recalculated for each study using the random-effects model, and a combined OR was calculated. RESULTS A total of 245 articles were obtained through an electronic search of health care databases. Thirteen studies examined the relationship between UC and smoking, whereas 9 examined the relationship between CD and smoking. We found evidence of an association between current smoking and CD (OR, 1.76; 95% confidence interval [CI], 1.40-2.22) and former smoking and UC (OR, 1.79; 95% CI, 1.37-2.34). Current smoking had a protective effect on the development of UC when compared with controls (OR, 0.58; 95% CI, 0.45-0.75). CONCLUSION This is the first meta-analysis, to our knowledge, to evaluate the relationship between smoking and IBD using accepted quality standards for meta-analysis reporting. Our meta-analyses confirm that smoking is an important environmental factor in IBD with differing effects in UC and CD. By using predefined inclusion criteria and testing for homogeneity, the current analysis provides an estimate of the effect of smoking on both these forms of IBD.

Newborn Screening: Toward a Uniform Screening Panel and System—Executive Summary

Abstract: The Maternal and Child Health Bureau commissioned the American College of Medical Genetics to outline a process of standardization of outcomes and guidelines for state newborn screening programs and to define responsibilities for collecting and evaluating outcome data, including a recommended uniform panel of conditions to include in state newborn screening programs. The expert panel identified 29 conditions for which screening should be mandated. An additional 25 conditions were identified because they are part of the differential diagnosis of a condition in the core panel, they are clinically significant and revealed with screening technology but lack an efficacious treatment, or they represent incidental findings for which there is potential clinical significance. The process of identification is described, and recommendations are provided.

Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases.

Abstract: Human mesenchymal stem cells (MSCs) are increasingly being considered in cell-based therapeutic strategies for regeneration of various organs/tissues. However, the signals required for their homing and recruitment to injured sites are not yet fully understood. Because stromal-derived factor (SDF)-1 and hepatocyte growth factor (HGF) become up-regulated during tissue/organ damage, in this study we examined whether these factors chemoattract ex vivo-expanded MSCs derived from bone marrow (BM) and umbilical cord blood (CB). Specifically, we investigated the expression by MSCs of CXCR4 and c-met, the cognate receptors of SDF-1 and HGF, and their functionality after early and late passages of MSCs. We also determined whether MSCs express matrix metalloproteinases (MMPs), including membrane type 1 (MT1)-MMP, matrix-degrading enzymes that facilitate the trafficking of hematopoietic stem cells. We maintained expanded BM- or CB-derived MSCs for up to 15-18 passages with monitoring of the expression of 1) various tissue markers (cardiac and skeletal muscle, neural, liver, and endothelial cells), 2) functional CXCR4 and c-met, and 3) MMPs. We found that for up to 15-18 passages, both BM- and CB-derived MSCs 1) express mRNA for cardiac, muscle, neural, and liver markers, as well as the vascular endothelial (VE) marker VE-cadherin; 2) express CXCR4 and c-met receptors and are strongly attracted by SDF-1 and HGF gradients; 3) express MMP-2 and MT1-MMP transcripts and proteins; and 4) are chemo-invasive across the reconstituted basement membrane Matrigel. These in vitro results suggest that the SDF-1-CXCR4 and HGF-c-met axes, along with MMPs, may be involved in recruitment of expanded MSCs to damaged tissues.

Putative contributors to the secular increase in obesity: exploring the roads less traveled

Abstract: Putative contributors to the secular increase in obesity: exploring the roads less traveled

CSIFT: A SIFT Descriptor with Color Invariant Characteristics

Abstract: SIFT has been proven to be the most robust local invariant feature descriptor. SIFT is designed mainly for gray images. However, color provides valuable information in object description and matching tasks. Many objects can be misclassified if their color contents are ignored. This paper addresses this problem and proposes a novel colored local invariant feature descriptor. Instead of using the gray space to represent the input image, the proposed approach builds the SIFT descriptors in a color invariant space. The built Colored SIFT (CSIFT) is more robust than the conventional SIFT with respect to color and photometrical variations. The evaluation results support the potential of the proposed approach.

Stem cell niches in the adult mouse heart

Abstract: Cardiac stem cells (CSCs) have been identified in the adult heart, but the microenvironment that protects the slow-cycling, undifferentiated, and self-renewing CSCs remains to be determined. We report that the myocardium possesses interstitial structures with the architectural organization of stem cell niches that harbor long-term BrdU-retaining cells. The recognition of long-term label-retaining cells provides functional evidence of resident CSCs in the myocardium, indicating that the heart is an organ regulated by a stem cell compartment. Cardiac niches contain CSCs and lineage-committed cells, which are connected to supporting cells represented by myocytes and fibroblasts. Connexins and cadherins form gap and adherens junctions at the interface of CSCs–lineage-committed cells and supporting cells. The undifferentiated state of CSCs is coupled with the expression of α4-integrin, which colocalizes with the α2-chain of laminin and fibronectin. CSCs divide symmetrically and asymmetrically, but asymmetric division predominates, and the replicating CSC gives rise to one daughter CSC and one daughter committed cell. By this mechanism of growth kinetics, the pool of primitive CSCs is preserved, and a myocyte progeny is generated together with endothelial and smooth muscle cells. Thus, CSCs regulate myocyte turnover that is heterogeneous across the heart, faster at the apex and atria, and slower at the base–midregion of the ventricle.

Minicolumnar abnormalities in autism

Abstract: Autism is characterized by qualitative abnormalities in behavior and higher order cognitive functions. Minicolumnar irregularities observed in autism provide a neurologically sound localization to observed clinical and anatomical abnormalities. This study corroborates the initial reports of a minicolumnopathy in autism within an independent sample. The patient population consisted of six age-matched pairs of patients (DSM-IV-TR and ADI-R diagnosed) and controls. Digital micrographs were taken from cortical areas S1, 4, 9, and 17. The image analysis produced estimates of minicolumnar width (CW), mean interneuronal distance, variability in CW (V (CW)), cross section of Nissl-stained somata, boundary length of stained somata per unit area, and the planar convexity. On average CW was 27.2 microm in controls and 25.7 microm in autistic patients (P = 0.0234). Mean neuron and nucleolar cross sections were found to be smaller in autistic cases compared to controls, while neuron density in autism exceeded the comparison group by 23%. Analysis of inter- and intracluster distances of a Delaunay triangulation suggests that the increased cell density is the result of a greater number of minicolumns, otherwise the number of cells per minicolumns appears normal. A reduction in both somatic and nucleolar cross sections could reflect a bias towards shorter connecting fibers, which favors local computation at the expense of inter-areal and callosal connectivity.

Polysomnographic characteristics in normal preschool and early school-aged children

Abstract: OBJECTIVE. The objective of this study was to describe overnight polysomnographic measures in normal children aged 3 to 7 years. We conducted a retrospective analysis of normal polysomnographic evaluations from participants in 2 large community-based studies of sleep-disordered breathing among preschoolers and early school-aged children at Kosair Children’s Hospital Sleep Medicine Research Center at the University of Louisville. Participants included 542 healthy children with ages ranging from 3.2 to 8.6 years. RESULTS. Subjects were excluded from analysis if they had documented snoring during polysomnography, an obstructive apnea-hypopnea index of ≥1.0, or a periodic leg-movement index of ≥5.0. Because the greatest differences in polysomnography occurred between ages 5 and 6 years, analyses were performed for children 3 to 5 years and for ages ≥6. Sleep cyclicity was distinct between age groups, with both showing an initial brief rapid-eye-movement period, which lengthened across the night, but only the older group showing a decrease in cycle length across the night. Average obstructive apnea indices were 0.03 per hour of total sleep time (TST) for 3- to 5-year-old children and 0.05 per hour of TST for ≥6-year-old children, whereas central apnea indices were 0.82 and 0.45 per hour of TST, respectively. Older children spent a greater percentage of sleep time supine, and the apnea-hypopnea index differed according to body position. Twenty percent of all subjects had end tidal carbon dioxide values of >45 mm Hg, and 2.2% had recorded values >50 mm Hg during ≥50% TST. High variance was present on all measures. CONCLUSIONS. Developmental changes occur in several polysomnographic measures among normal children from 3 to 7 years of age, particularly during transition from preschool to early school age. Our findings in a large number of healthy community children comprise the most extensive compilation of normative reference values for laboratory-based pediatric polysomnography to date.

Cerebral palsy: an overview.

Abstract: The presentation of cerebral palsy can be global mental and physical dysfunction or isolated disturbances in gait, cognition, growth, or sensation. It is the most common childhood physical disability and affects 2 to 2.5 children per 1,000 born in the United States. The differential diagnosis of cerebral palsy includes metabolic and genetic disorders. The goals of treatment are to improve functionality and capabilities toward independence. Multispecialty treatment teams should be developed around the needs of each patient to provide continuously updated global treatment care plans. Complications of cerebral palsy include spasticity and contractures; feeding difficulties; drooling; communication difficulties; osteopenia; osteoporosis; fractures; pain; and functional gastrointestinal abnormalities contributing to bowel obstruction, vomiting, and constipation. Valid and reliable assessment tools to establish baseline functions and monitor developmental gains have contributed to an increasing body of evidenced-based recommendations for cerebral palsy. Many of the historical treatments for this ailment are being challenged, and several new treatment modalities are available. Adult morbidity and mortality from ischemic heart disease, cerebrovascular disease, cancer, and trauma are higher in patients with cerebral palsy than in the general population.

Inhaled nitric oxide in preterm infants undergoing mechanical ventilation.

Abstract: Background Bronchopulmonary dysplasia in premature infants is associated with prolonged hospitalization, as well as abnormal pulmonary and neurodevelopmental outcome. In animal models, inhaled nitric oxide improves both gas exchange and lung structural development, but the use of this therapy in infants at risk for bronchopulmonary dysplasia is controversial. Methods We conducted a randomized, stratified, double-blind, placebo-controlled trial of inhaled nitric oxide at 21 centers involving infants with a birth weight of 1250 g or less who required ventilatory support between 7 and 21 days of age. Treated infants received decreasing concentrations of nitric oxide, beginning at 20 ppm, for a minimum of 24 days. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age. Results Among 294 infants receiving nitric oxide and 288 receiving placebo birth weight (766 g and 759 g, respectively), gestational age (26 weeks in both groups), and other characteristics were sim...

The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis.

Abstract: Proper response of normal stem cells (NSC) to motomorphogens and chemoattractants plays a pivotal role in organ development and renewal/regeneration of damaged tissues. Similar chemoattractants may also regulate metastasis of cancer stem cells (CSC). Growing experimental evidence indicates that both NSC and CSC express G-protein-coupled seven-transmembrane span receptor CXCR4 and respond to its specific ligand alpha-chemokine stromal derived factor-1 (SDF-1), which is expressed by stroma cells from different tissues. In addition, a population of very small embryonic-like (VSEL) stem cells that express CXCR4 and respond robustly to an SDF-1 gradient was recently identified in adult tissues. VSELs express several markers of embryonic and primordial germ cells. It is proposed that these cells are deposited early in the development as a dormant pool of embryonic/pluripotent NSC. Expression of both CXCR4 and SDF-1 is upregulated in response to tissue hypoxia and damage signal attracting circulating NSC and CSC. Thus, pharmacological modulation of the SDF-1-CXCR4 axis may lead to the development of new therapeutic strategies to enhance mobilization of CXCR4+ NSC and their homing to damaged organs as well as inhibition of the metastasis of CXCR4+ cancer cells.

Neural mechanisms in Williams syndrome: a unique window to genetic influences on cognition and behaviour.

Abstract: Williams syndrome is a rare neurodevelopmental disorder with a distinct behavioural and neuropsychological profile. Meyer-Lindenberget al. describe new research relating structural and functional differences to the underlying genetics of this disorder and their influence on cognition and behaviour. Williams syndrome, a rare disorder caused by hemizygous microdeletion of about 28 genes on chromosome 7q11.23, has long intrigued neuroscientists with its unique combination of striking behavioural abnormalities, such as hypersociability, and characteristic neurocognitive profile. Williams syndrome, therefore, raises fundamental questions about the neural mechanisms of social behaviour, the modularity of mind and brain development, and provides a privileged setting to understand genetic influences on complex brain functions in a 'bottom-up' way. We review recent advances in uncovering the functional and structural neural substrates of Williams syndrome that provide an emerging understanding of how these are related to dissociable genetic contributions characterized both in special participant populations and animal models.

Environmental Cardiology Studying Mechanistic Links Between Pollution and Heart Disease

Abstract: Environmental factors are considered key determinants of cardiovascular disease. Although lifestyle choices such as smoking, diet, and exercise are viewed as major environmental influences, the contribution of pollutants and environmental chemicals is less clear. Accumulating evidence suggests that exposure to pollutants and chemicals could elevate the risk of cardiovascular disease. Many epidemiological studies report that exposure to fine particles present in ambient air is associated with an increase in cardiovascular mortality. Statistically significant relationships between particulate air pollution and ischemic heart disease, arrhythmias, and heart failure have been reported. Animal studies show that exposure to ambient air particles increases peripheral thrombosis and atherosclerotic lesion formation. Exposures to arsenic, lead, cadmium, pollutant gases, solvents, and pesticides have also been linked to increased incidence of cardiovascular disease. Mechanistically, these effects have been attributed to changes in the synthesis or reactivity of nitric oxide that may be caused by environmental oxidants or increased endogenous production of reactive oxygen species. Additional studies are urgently needed to: identify the contribution of individual pollutants to specific aspects of cardiovascular disease; establish causality; elucidate the underlying physiological and molecular mechanisms; estimate the relative susceptibility of diseased and healthy individuals and that of specific population groups; and determine whether pollutant exposure are risk correlates, that is, whether they influence major risk factors, such as hypertension, cholesterol, or diabetes, or whether they contribute to the absolute risk of heart disease. Collectively, these investigations could contribute to the emergent field of environmental cardiology.

A genetic algorithm approach to developing the multi-echelon reverse logistics network for product returns

Abstract: Traditionally, product returns have been viewed as an unavoidable cost of doing business, forfeiting any chance of cost savings. As cost pressures continue to mount in this era of economic downturns, a growing number of firms have begun to explore the possibility of managing product returns in a more cost-efficient manner. However, few studies have addressed the problem of determining the number and location of centralized return centers (i.e., reverse consolidation points) where returned products from retailers or end-customers were collected, sorted, and consolidated into a large shipment destined for manufacturers’ or distributors’ repair facilities. To fill the void in such a line of research, this paper proposes a nonlinear mixed-integer programming model and a genetic algorithm that can solve the reverse logistics problem involving product returns. The usefulness of the proposed model and algorithm was validated by its application to an illustrative example dealing with products returned from online sales.